Living bodies have a function to prevent and inhibit the occurrence of autoimmune diseases, and this function is referred to as the “immune modulatory function”. NKT cells recently attracted attention as a lymphocyte having the “immune modulatory function”. (Saishin Igaku Vol. 55, No. 4, pp. 858-863.) The inventors have been working on the development of medicines that act upon NKT cells (a pharmaceutical drug material that appropriately stimulates NKT cells and effectively expresses their immune modulatory function).
The conventional treatment methods for autoimmune diseases focused mainly on “non-specific immunosuppressive therapy” involving glucocorticoids and immunosuppressants. “Non-specific immunosuppressive therapy” refers to methods of treatment that suppress many of the biological functions of immune cells without special selectivity and distinction. These methods of treatment, therefore, suppress biological reactions inducing and aggravating diseases but they also suppress biological reactions necessary to living bodies (side effects). Therefore, the development of specific immunosuppressants (pharmaceutical drug agents that suppress only the biological reactions that induce and aggravate diseases) is urgently desired. Auto-antigen peptide treatments were recently tested with this goal in mind. However, since peptides are manifested by the major histocompatibility gene complex (MHC) molecules that have individual differences, the difference in efficacy varied tremendously among individuals, and allergic reactions also posed a problem.
Alpha-galactosylceramide has been identified so far as a substance capable of stimulating NKT cells by other researchers. [Science, Vol. 278, pp. 1626-1629 (1997), Proc. Natl. Acad. Sci. USA Vol. 95, pp. 5690-5693 (1998), J. Med. Chem. 1995, 38, pp. 2176-2187, Japanese Patent Application Public Disclosure (Kokai) Hei 5-9193, Japanese Patent Application Public Disclosure (Kokai) Hei 5-59081, Japanese Patent No. 3088461 and U.S. Pat. No. 5,936,076.] The inventors administered the alpha-galactosylceramide described in the publications to treat autoimmune diseases such as the animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), and collagen induced arthritis, the animal model of rheumatoid arthritis. However, this alpha-galactosylceramide induces both IL-4, a cytokine that suppresses autoimmune diseases, as well as IFN-γ, a cytokine that aggravates autoimmune diseases. Therefore, this alpha-galactosylceramide was found to be clearly not effective in suppressing or treating autoimmune diseases. (American Immunology Society Journal, the Journal of Immunology, Jan. 1, 2001, Vol. 166, pp. 662-669.) That is, conventional alpha-galactosylceramide is not an appropriate medicine for autoimmune disease since it induces a simultaneous manifestation of conflicting functions (a function to suppress disease and a function to aggravate the disease) of NKT cells.